The research is directed to the origin and spatiotemporal distribution of interacting systems that determine the outgrowth and pattern of symmetry of the vertebrate limb. Some interactions, already identified, control the emergence of changing morphogenetic patterns along, respectively, each of the three coordinate limb axes, and affect patterns of cellular necrosis. They involve both epithelial and mesenchymal components of the prospective limb and the paraxial mesoderm. The nature of these interactions and the mechanisms of their morphogenetic effects will be sought. The existence of hitherto unrecognized interacting systems will be probed. The effects of embryonic aging on the time span and efficacy of the systems will be analyzed. Anticipated results will provide new insights into the control of limb development and deformity and will suggest new approaches relative to the general problems of control of the epigenesis of morphological patterns. The latter is an area notably lacking in a fruitfull conceptual relationship with molecular biology, on the one hand, and developmental anatomy on the other. Procedures will heavily involve dissociation and recombination of tissues and of cells, cellular sorting, and tests of morphogenetic performance of recombinants in vitro and in various intraembryonic grafts. Extracts and homogenates of morphogentically significant tissues and cells, and medium conditioned by them, will be tested for specific morphogenetic effects. Radioactive labeling of morphogenetically significant molecules will be involved. Transmission and scanning electron microscopy will be used to probe for significant ultrastructure features involved in interaction between cells and between tissues.